Bone Physiology Flashcards
Protein in the bone matrix is >90%
Collagen
Most abundant cells found in the compact bone are the
Osteocytes
An osteoblast becomes an osteocyte when it
Gets trapped in the bone matrix it has secreted
Two varieties of bone:
- Compact2. Trabecular
Common site of bone growth, particularly long bones
Epiphysial Plate
Three processes that halt bone growth
- Epiphyses unite with shaft (epiphysial closure)2. Cartilage cells stop proliferating3. VEGF secreted -> vascularization/ ossification
Three most important hormone regulators of Calcium in the blood
Parathyroid Hormone (PTH), Vitamin D, calcitonin
Transcription Factor associated with osteoblast precursor cells
RUNX 2
In mice, knocking out RUNX2 led to
Non-ossification of bones (osteoblasts not maturing) -> floppy mice!
Products and enzymes that identify an osteoblast as active
Collagen, Alkaline phosphatase, osteoprotegerin (OPG), RANK ligand
These 2 factors from osteoblasts stimulate maturation of an active osteoclast
RANK LIGAND and OPG
“Decoy” OPG can bind ________ to inhibit osteoclast differentiation
RANK Ligand
In osteoporosis, estrogen replacement therapy will upregulate _____ to inhibit osteoclast activity
OPG
Full bone replacement occurs, on average, every
10 years
Most of the bodys calcium is in (body part)
Bone (98%)
Physiologic roles of Calcium
- Bone formation
- Neuronal excitability
- NT release
- Muscle contraction
- Membrane integrity
- Blood Coagulation
Hypocalcemia can lead to:
- Tetany (increased permeability of neurons to Na+, more action potentials, muscle spasm)
- Parasthesias (things feel funny)
- Muscle cramps
- Convulsions
- Laryngospasms
Hypercalcemia leads to:
Anorexia, Nausea, (GI symptoms basically), lethargy, coma
In most cases Calcium and Phosphate are co-regulated, except in
the kidney
(they are regulated in opposite directions)
Causes of hypercalcemia
Hyperparathyroidism
Cancer
Causes of hypocalcemia
Hypoparathyroidism
Vitamin D Deficiency
Chronic Kidney disease (cant reabsorb in tubules)
Calcium malabsorption
How does Vitamin D moderate calcium
Pulls in Ca2+ from gut
Mechanism of Phosphorous entrance/exit from body (what mediates)
Phosphorous pulled in from gut w/ help from transporter upregulated by Vitamin D
Filtered in glomerulus, most reabsorbed.
PTH can inhibit resorption transporter (block P, leaves via urine)
Causes of hypophosphatemia
Inadequate P absorption (gut disorder or Vitamin D deficiency)
Excessive renal excretion (renal disease/renal failure)
Hyperparathyroidism (too much PTH made, leads to blockage of resabsorption at kidney -> pee too much out)
Phosphorous necessary for:
energy (ATP), active enzymes and proteins
Causes of hyperphosphatemia
Impaired glomerular filtration (cant get P out of blood)
Hypoparathyroidism (PTH not present, too much resorption of P at tubule)
What is PTHrP and what does it do?
Protein associated with PTH, binds to the same receptor, though they are usually found in separate places
Produced as a “paracrine” hormone in tissues local to the receptor.
A kind of developmental hormone
- Stimulates cartilage cells to proliferate and maintain proliferative state (used both in utero bone formation and after birth)
- In brain, PTHrP inhibits excitotoxic damage to developing neurons
- Critical to teeth eruption
In normal circumstances, what is the body’s response to low serum calcium?
Parathyroid glands produce more parathyroid hormone, which increases calcium reabsorption in the kidneys.
Increase in Vitamin D formation (via liver and kidney) that will “pull in” more calcium from gut.
Possible to get bone resorption, but much less common in non-pathogenic people
1,25 OHD (Vitamin D) binds to transcalciferin [TC] and then acts on which part of the cell
In the Nucleus, binds to the RXR (retanoic acid receptor), which turns off repressors, recruits activators, and turns on the needed genes to get calcium into the blood
Vitamin D increases _ _, _ _, and _ _ to increase absorption of Calcium from gut and increases expression of enzymes to increase Ca retention at kidney
Calbindins, Ca ATPases, TRPV6 (transporter across lumen)
Why would inactive Vitamin D be made?
Plasma calcium too high. As it is being processed, vitamin D shunted towards inactive form until balanced
Where is calcitonin made?
Parafollicular Cells in the Thyroid
What does calcitonin do, broadly?
Decreases bone breakdown
Increases excretion of calcium from kidney
Ultimately wants to reduce serum calcium
What does calcitonin block?
Blocks osteoclasts from breaking down bone (and thus releasing calcium into blood).
What is the effect of estrogen on osteoclasts?
estrogen inhibits secretion of interleukins/ enzymes (IL-1, IL-6, TNF alpha) associated with development of osteoclasts
Upregulates OPG to bind RANK ligand and inhibit osteoclast development
Stimulates production of TNF beta that causes osteoclast apoptosis
Disorders of bone mineral homeostasis (4)
Osteoporosis- overactive osteoclasts due to low estrogen)
Osteomalacia (or ricketts)- inadequate mineralization of bones due to Vitamin D deficiency
Osteopetrosis- unopposed osteoblasts (osteoclasts not breaking down, leads to “rock bones”)
Pagets Disease- osteoclasts work abnormally in weird places, leads to abnormal bone remodeling (weird faces)
